The objectives of this research are to elucidate the mechanisms by which copper: is transported into liver cells, mobilized and utilized intracellularly and secreted from a liver cell. This research is coupled to experiments on the molecular basis of Wilson's Disease and Menkes' Disease. Classic enzyme-kinetic approaches are used to characterize uptake and efflux mechanisms with isolated hepatocytes. Similar experiments are also done on cells isolated from the animal model for Menkes' Disease. We are also examining possible roles of metals in the regulation of metalloprotein synthesis. Copper deprivation stimulates the synthesis of a cytosolic form of Mn-superoxide dismutase in cultures of D. dendroides. Experiments are in progress to probe the mechanism of this effect. From the same system, the roles of two low molecular weight copper proteins on the activation of apo-copper enzymes are also being examined.